Opioids

Question 1

Nociception-

Answer 1

“non conscious neural traffic due to (potential ) trauma to tissue.”

touch something hot, you pull your muscle away

Question 2

Pain-

Answer 2

“complex, unpleasant awareness of sensation modified by experience, expectation, immediate context and culture”.
phantom pain, based on memories

Question 3

steps of pain

Answer 3

1. Nociceptors stimulated
2. Release of Substance P and Glutamate
3. Afferent nerve stimulated (a delta fibers- sharp pain, c fibers- unmyelated dull pain, travels slower, needs more stimulation)
4. Fibres decussate
5. Action potential ascends
6. Synapse in thalamus
7. Project to Post central gyrus

Question 4

peripheral pain modulation

Answer 4

tissue damage sends inhibitory to s. gelatinous. rub it better by A beta fibers are activated, stimulate s. gelatinous, s. gelatinous sends inhibitory signals

Question 5

central pain modulation

Answer 5

thalamus and cortex can stimulate periaqueductal grey matter, that sends inhibitory signals via endogenous opioids

Question 6

Endogenous Opioids:

Answer 6

• Enkephalins
• Dynorphins
• B-endorphins

Question 7

Opioid receptors

Answer 7

G protein receptors

• MOP/μ – most important clinically • DOP/δ • KOP/Κ

Question 8

MOP receptor

Answer 8

found in brainstem and thalamus
responsible for therapeutic and adverse effects
GPCR: • Agonist binds • decrease in cAMP • Efflux of potassium • Hyperpolarisation of membrane • Decreases substance P and GABA release • Increases dopamine release, decreasing pain response

Question 9

Phosphorylation and uncoupling causing opioid tolerance

Answer 9

opioid binds, decreased cAMP, intracellular Phosphorylation by kinases, this changes receptors, arresting can bind to receptor and displace the G protein, or opioid may not have the same effect as they can’t bind as well.

Question 10

cAMP production causing opioid tolerance

Answer 10

opioids bind to receptor, decrease cAMP, when remove opioid, increased cAMP.
either decrease the time between doses, or increase each dose. neural excitability is caused by increased cAMP, causing withdrawal symptoms.

Question 11

basics of opioids

Answer 11

• Exploit natural opioid receptors either agonise or antagonise
• Main therapeutic effects via μ-receptors
• Aim to modulate pain
• Also indicated in- cough, diarrhoea, palliation

Question 12

morphine

Answer 12

• PO, IV, IM, SC, PR • Gut absorption erratic • Significant first pass effect- 40% oral bioavailability
• Rapidly enters all tissues including foetal, lipophilic • Struggles to cross blood- brain barrier, not protein bindings, not the best cos effects
elimination RENALLY

Question 13

X^ morphine

Answer 13

Strong affinity to μ receptors., • Analgesia, Euphoria
#:• Respiratory Depression (main cause of death in OD) • Emesis • GI tract • Cardiovascular • Miosis • Histamine release- caution in asthmatics
X: renal impairment

Question 14

fentanyl

Answer 14

• IV, Epidural, Intrathecal, Nasal • 80-100% bioavailability
• Highly lipophilic, highly protein bound • High level of CNS crossing
• Hepatic via CYP3A4
• Half life 6 minutes • Renally excreted

Question 15

fentanyl, #X,

Answer 15

100x more potent than morphine, higher affinity for receptors, less histamine: sedation, constipation
action: analgesia, anaesthetic,
#• Respiratory Depression • Constipation • Vomiting
X: renal imp., less toxic than kidneys

Question 16

codeine

Answer 16

PO, SC administration
• Codeine to Morphine via CYP2D6 • CYP2D6 inhibited by Fluoxetine(SSRI) • Variable expression
renal excretion

Question 17

codeine potency, action, #

Answer 17

1/10th potency to morphine
mild-moderate analgesia, cough depressant
#: constipation, resp depression, worsen children

Question 18

mixed agonist- antagonist example and metabolism

Answer 18

buprenorphine,
transdermal, buccal, sublingual, very lipophilic, hepatic metabolism via CYP3A4, biliary excretion, safe in renal imp. had life is long

Question 19

buprenorphine potency, #, actions

Answer 19

very high affinity to receptor, long duration of action, not easily displaced, lower efficacy,
action; moderate to severe pain, opioid replacement treatment
#: • Respiratory depression • Low BP • Nausea • Dizziness

Question 20

antagonist of opioids for OD

Answer 20

naloxone
IV, IM, intranasal, PO, low oral bioavailability, rapid onset of action
very lipophilic,
renal excreted

Question 21

naloxone potency, action, #

Answer 21

• Greater affinity than morphine • Affinity less than buprenorphin
 Competitive antagonism of opioid, overdose treatment
#: • Short half life • Slow infusion,

Question 22

X opioids

Answer 22

special considerations:• Manual labourers/Drivers • Elderly • Bedbound • Asthmatics • Biliary tract obstruction • Respiratory Diseases • Renal impairment • Pregnancy
contraindication: • Hepatic failure • Acute respiratory Distress • Comatose • Head injuries • Raised ICP

Question 23

Palliative prescribing

Answer 23

Buprenorphine, diamorphine, fentanyl, morphine and oxycodone
Indications: Pain, Shortness of breath • Manage side effects: nausea, constipation
• Months to Weeks
• Long acting background level of pain control
• Short acting top up doses for extra • Days to Hours
• Continuous subcut infusion
• Top up doses as needed